The present invention, in some embodiments thereof, relates to immunoparticles and methods of generating and using same.
Liposomes are useful drug delivery vehicles since they may protect encapsulated drugs from enzymatic degradation and rapid clearance in vivo, or alter biodistribution, potentially leading to reduced toxicoties. A major limitation to the development of many specialized applications is the problem of directing liposomes to tissues where they would not normally accumulate. Consequently a great deal of effort has been made over the years to develop liposomes that have targeting moieties attached to their surface. These targeting moieties have included ligands, such as oligosaccharides, peptides, proteins and vitamins. Most studies have focused on antibody conjugation since procedures for producing monoclonal antibodies against a tissue target of interest are well established.
Numerous procedures for the conjugation of antibodies to liposomes have been developed. These fall into four general categories defined by the particular functionality of the antibody being modified, namely amine modification, carbohydrate modification, disulfide modification and non-covalent conjugation. However most of these approaches result in loss of antibody variable region structure which results in loss of binding activity. In addition, current procedures for generating immunoliposomes are inefficient resulting in loss of precious amounts of antibody.
Indirect methods for generating immunoliposomes using receptor-ligand-like systems are known. For, example, liposome avidin conjugates have been shown to effectively target biotinylated antibodies to known cell/tissue surface antigens. However, such an approach requires both modifications of the antibody (e.g., biotinylation) and the liposomes (avidin), which again may hamper antibody functionality.
A similar approach has frequently been used with protein A/G-liposome conjugates targeted to the Fc chain of antibodies. This approach, is not suitable for in vivo applications because of competition from the general IgG population.
Review of the field is available by Ansell et al. Methods in Molecular Medicine, Vol 25: Drug Targeting: Strategies, Principles and Applications Edited by: G. E. Francis and C. Delgado© Humana Press, Inc., ToTowa, Nj.
Leserman et al. 1980 Nature 288:602-604 teaches targeting of fluorescent liposomes covalently coupled with monoclonal antibody or protein A to cells precoated with an antibody. Like protein A/G this approach, is not suitable for in vivo applications because of competition from the general IgG population.
Additional Related Art:
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